Peptide hormones act as messengers on target tissues stimulating the target organ to respond to a physiological conditions sensed, directly or indirectly, from the brain. A variety of diseases are known to result from abnormalities in the quantity, stability, or activity of indigenously produced peptide hormones. Some types of these diseases are amenable to treatment by hormone supplementation. Peptide hormones, classically isolated from natural sources, are currently produced using recombinant DNA technology making such hormones commercially available for the treatment of a variety of diseases.
The mechanism of action of peptide hormones and their corresponding therapeutic potential cannot be divorced from the complex cascade which mediates their action. Maintenance of the balance between synthesis and catabolism, activation and repression or energy usage and storage allow the organism to adapt to environmental stress but return to a basal state once the stimulus is removed. The instant invention provides a protein, the porcine vasoactive intestinal peptide (pVIP) receptor whose activity is intimately tied to vasodilative effects in lung, gastrointestinal tract and possibly some other tissues.
A number of G-protein coupled receptors have been cloned, for example, the receptors for mouse gonadotropin release hormone (Tsutsumi, et al., 1991, Molecular Endocrinology 6:1163-1169), adenylate cyclase activating polypeptide (Arimura, A., 1992, TEM 3:288-294, lutropin-choriogonadotropin (McFarland, et al., 1989, Science 245:494-499), thyrotropin releasing hormone (Zhao, et al., 1992, Endocrinology 130:3529-3536), human and rat dopamine (Zhou, et al., 1990, Nature 342:76-80), glucagon-like peptide 1 (Thorens 1992, PNAS 89:8641-8645), calcitonin (Lin, et al., 1991, Science 254:1022-1024) parathyroid hormone and parathyroid hormone-related peptide (Abou-Samra, et al., 1992, PNAS 89:2732-2736), endothelin 1 (Lin, et al., 1991 PNAS 88:3185-3189), secretin (Ishihara, et al., 1991, EMBO J. 10:1635-1641), and rat vasoactive intestinal peptide (Ishihara et al., 1992, Neuron 8:811-819).
This invention establishes the precise identity of the porcine pVIP receptor. The present invention also provides methods to purify the pVIP receptor and DNA sequences encoding same, and to produce useful quantities of each using recombinant DNA techniques. This and other objects of the instant invention will be apparent from the specification as a whole.